DESCRIPTION (Applicant's Abstract): After more than a decade of research and controversy, it has been conclusively demonstrated that Helicobacter pylori is the main cause of peptic ulcer disease. High infection rates around the world pose serious health and economic problems. In the U. S. alone, 500,000 new cases, and 4 million recurrences are reported annually, at a cost of $3 to $4 billion dollars. Current therapies for H. pylori infections consist of combinations of antibiotics, and H2 blockers. However, due to the serious adverse reactions, patient compliance is low, leading to the development of antibiotic resistance. Thus, new approaches to the treatment H. pylori infections are urgently needed. For thousand of years traditional systems of medicine have successfully used botanicals (plant-based medicines) for the treatment of dyspepsia, gastritis and peptic ulcers. However, most of these botanicals have not been systematically screened for anti-H. pylori activity. This proposal describes an international, multidisciplinary approach to investigating botanical extracts for the treatment and prevention of H. pylori infections. The work is designed to generate sufficient preliminary data to serve as the basis of more definitive studies. The major goal of the project is to identify and standardize botanical extracts and combinations of extracts for the treatment of H. pylori infections. To accomplish this goal, the project involves (1) selection and procurement of botanicals to be tested (2) extraction of the source materials, (3) short-term in vitro and fn vivo testing biological studies to determine activity and mechanistic information (4) in vivo evaluations to establish safety and efficacy, and (5) determination of the major chemical constituents for standardization of the active extracts. Over the two-year period, approximately 60 new botanicals will be selected and evaluated for antibacterial activity against H. pylori. The list of high priority botanicals for testing will be generated based on data analysis from the Napralertsm database, Medline, German Commission E Monographs and other data sources. The success of this method for plant selection is seen in our preliminary results where an initial testing of 25 identified botanicals led to 13 active extracts. In this project, the botanicals will be procured and extracts prepared. The botanical extracts will be subjected to in vitro bioassay protocols using 15 H. pylori strains. Active extracts will be utilized for in vivo studies. The long-term objectives are to develop safe and effective botanical extracts for the treatment and prevention of H. pylori infections.